Miso, fermented soybean paste, suppresses high-fat/high-sucrose diet-induced muscle atrophy in mice.

This study investigated the effects of miso, a traditional fermented soybean food in Japan, on muscle mass atrophy. Eight week old male C57BL/6J mice were fed high fat/high sucrose diet with or without miso for 12 weeks. A miso diet increased soleus muscle weights (p<0.05) and reduced intraperitoneal glucose tolerance and insulin tolerance (p<0.05). The miso diet downregulated the Tnfα and Ccl2 expression, related to inflammation, and Trim63 and Fbxo32 expression, related to muscle atrophy, in the soleus muscle (p<0.05). The miso diet increased short-chain fatty acids levels, including acetic, propanoic, and butanoic acids, in the feces, serum, and soleus muscle (p<0.05). According to the LEfSe analysis, the miso diet increased family Prevotellaceae, family Christensenellaceae, family Dehalobacterium, family Desulfitibacter; family Deferribacteraceae, order Deferribacterales, class Deferribacteres; and family Gemmatimonadaceae, order Gemmatimonadetes, and class Gemmatimonadales, whereas the miso diet decreased family Microbacteriaceae, order Micrococcales, class Actinobacteria, and family Lactobacillaceae. Miso suppressed high fat/high sucrose diet induced impaired glucose tolerance, low muscle strength, and muscle atrophy by improving dysbiosis and increasing short-chain fatty acids production and provides new insights into the preventive effects of fermented foods on sarcopenia.

Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study.

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1ß-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1ß-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints.

Association of Estimated Salt and Miso Intake with the Prevalence of Obesity in People with Type 2 Diabetes: A Cross-Sectional Study.

Salt intake is often estimated by the amount of sodium excreted in urine, and miso has been reported to increase it. This cross-sectional study investigated the relationship between obesity and high estimated salt intake with and without habitual miso consumption. Estimates of salt intake (g/day) were calculated using urinary sodium excretion, and a high estimated intake was defined as greater than the median amount of 9.5 g/day. Participants were divided into four groups based on estimated salt intake and miso consumption. Among 300 people, the proportions of obesity were 77.8% (n = 14/18), 40.2% (n = 53/132), 26.0% (n = 33/127), and 34.8% (n = 8/23) in the (+/-), (+/+), (-/+), and (-/-) groups of high estimated salt intake/habitual miso consumption, respectively. Compared with the (+/-) group, the adjusted odds ratios for obesity were 0.07 (95% confidence interval (CI): 0.02-0.26, p < 0.001), 0.16 (95% CI: 0.03-0.76, p = 0.022), and 0.14 (95% CI: 0.04-0.51, p = 0.003) in the (-/+), (-/-), and (+/+) groups, respectively. The presence of obesity was not much higher in people with high estimated salt intake with habitual miso consumption than that in people without. Clinicians should be aware that miso consumption promotes salt excretion, which may lead to an apparently higher estimated salt intake than actual.

Habitual Miso (Fermented Soybean Paste) Consumption Is Associated with Glycemic Variability in Patients with Type 2 Diabetes: A Cross-Sectional Study.

Glycemic control, including glycemic variability, is important for the prevention of diabetic vascular complications in patients with type 2 diabetes mellitus (T2DM). There was an association between miso soup intake and insulin resistance. However, the relationship between habitual miso consumption and glycemic control, including glycemic variability, in patients with T2DM remains unknown. We defined people without habitual miso consumption if they did not consume miso soup at all in a day. The average, standard deviation (SD), and coefficient of variation (CV), calculated as CV = (SD/average HbA1c) × 100 (%), of hemoglobin (Hb) A1c levels were evaluated. The proportions of habitual miso consumption of male and female were 88.1% and 82.3%, respectively. The average (7.0 [6.4-7.5] vs. 7.3 [6.8-8.4] %, p = 0.009), SD (0.21 [0.12-0.32] vs. 0.37 [0.20-0.72], p = 0.004), and CV (0.03 [0.02-0.04] vs. 0.05 [0.03-0.09], p = 0.005) of HbA1c levels in female with habitual miso consumption were lower than those of female without. Moreover, habitual miso consumption correlated with average (ß = -0.251, p = 0.009), SD (ß = -0.175, p = 0.016), and CV (ß = -0.185, p = 0.022) of HbA1c levels after adjusting for covariates. However, no association between habitual miso consumption and any glycemic parameters was shown among male. This study clarified the association between habitual miso consumption and good glycemic control, including glycemic variability, in female, but not in male.

Short energy intake is associated with muscle mass loss in older patients with type 2 diabetes: A prospective study of the KAMOGAWA-DM cohort.

BACKGROUND & AIM: Past studies reported that the intake of adequate energy is more important than protein intake; however, the relationship between energy intake and muscle mass loss remains unclear thus far. This study therefore explored the association between energy intake and muscle mass loss in people with type 2 diabetes (T2D). METHODS: In this prospective cohort study, impedance body composition and a brief-type self-administered diet history questionnaire were used for analyzing body composition and habitual diet intake, respectively. Skeletal muscle mass index (SMI, kg/m2) was defined as appendicular muscle mass (kg) ÷ height-squared (m2). Rate of SMI change (%) was calculated as ([SMI at baseline - SMI at follow-up]/[follow-up duration (years) × baseline SMI (kg/m2)]) × 100, and muscle mass loss was defined as rate of SMI change ≥0.5%. Energy intake was defined as total energy intake (kcal/day) divided by ideal body weight (kg), defined as 22 × patient height-squared (m2). RESULTS: Among non-older and older participants, 54.8% (n = 51/93) and 58.9% (n = 116/197) experienced muscle mass loss at 16.3 (6.4) and 18.1 (7.1) months' follow-up, respectively. Logistic regression analyses showed that energy intake was associated with incident muscle mass loss after adjusting for age, sex, insulin, sodium glucose cotransporter-2 inhibitor, glucagon-like peptide-1 agonist, steroids, smoking, exercise, alcohol intake, body mass index, SMI, presence of renal failure, and protein intake (g/actual body weight/day) in the older people (odds ratio [OR] 0.94 [95% confidence interval [CI] 0.88-0.996], p = 0.037), whereas energy intake was not associated with incident muscle mass loss in the non-older people (OR 0.96 [95% CI 0.86-1.06], p = 0.423). CONCLUSIONS: Insufficient energy intake is associated with muscle mass loss in older people with T2D. Therefore, it is recommended to consume enough energy for older people with T2D to keep muscle mass.

Reduced dietary omega-3 fatty acids intake is associated with sarcopenia in elderly patients with type 2 diabetes: a cross-sectional study of KAMOGAWA-DM cohort study.

Omega-3 fatty acids intake is important to maintain muscle mass. However, the relationship between omega-3 fatty acids intake and sarcopenia in elderly patients with type 2 diabetes has been unclear. We used the brief-type self-administered diet history questionnaire for the assessment of habitual food and nutrient intake. Body composition of patients was evaluated using bioimpedance analysis. To investigate the effect of energy intake on the presence of sarcopenia, we performed logistic regression analyses. Among the patients, 45 patients (13.2%) were diagnosed as sarcopenia. Patients with sarcopenia were aged [74.2 (5.7) vs 71.4 (5.9) years, p = 0.003] and lower body mass index [21.2 (3.5) vs 24.3 (4.6) kg/m2, p<0.001] than those without. In addition, omega-3 fatty acids intake of patients with sarcopenia was lower than that without [2.6 (1.0) vs 3.0 (1.2) kcal/day, p = 0.046]. Omega-3 fatty acids intake was negatively associated with the presence of sarcopenia (odds ratio: 0.29, 95% confidence interval: 0.14-0.60, p<0.001) after adjusting for age, sex, exercise, smoking status, diabetes duration, hemoglobin A1c, energy intake, protein intake, fat intake and omega-3 fatty acids intake. Omega-3 fatty acids intake was negatively associated with the presence of sarcopenia in elderly patients with type 2 diabetes.

High brain natriuretic peptide is associated with sarcopenia in patients with type 2 diabetes: a cross-sectional study of KAMOGAWA-DM cohort study.

Association between heart failure and sarcopenia has been reported, however, the association between sarcopenia and brain natriuretic peptide (BNP) is unclear. Thus, we investigated the association between sarcopenia and BNP in type 2 diabetic patients without heart failure. In this cross-sectional study, skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass, measured by bioimpedance analyzer, by the square of the height. Sarcopenia was defined as having both handgrip strength of <26 kg for men and <18 kg for women, and SMI of <7.0 kg/m2 for men and <5.7 kg/m2 for women. To investigate the impact of BNP levels on the presence of sarcopenia, propensity-score matching analysis was used to remove the bias of confounding variables, including age, sex, duration of diabetes, body mass index, exercise, systolic blood pressure, smoking status, hemoglobin A1c, creatinine, energy and protein intake. The area under the curve (AUC) of BNP levels for the presence of sarcopenia was calculated by the receiver operating characteristic curve (ROC). Among 433 patients (236 men and 65.4 (11.1) years), 32 patients (7.4%) were diagnosed as sarcopenia. In the propensity-matched 58 patients, BNP levels (Δ10 pg/mL incremental) were associated with the presence of sarcopenia by logistic regression analysis, (odds ratio: 1.56, 95% confidence interval: 1.14-2.13, p = 0.002). The optimal cut-off point of BNP levels for sarcopenia is 27.3 pg/mL (AUC 0.777, 95%CI, 0.691-0.863, sensitivity = 0.813, specificity = 0.736, p < 0.001). In conclusion, BNP levels were associated with sarcopenia in type 2 diabetic patients without heart failure.

Shortage of energy intake rather than protein intake is associated with sarcopenia in elderly patients with type 2 diabetes: A cross-sectional study of the KAMOGAWA-DM cohort.

BACKGROUND: Energy intake is important for the maintenance of muscle mass. The relationship between energy intake and sarcopenia in elderly patients with type 2 diabetes (T2D) has been unclear. METHODS: Using a brief-type self-administered diet history questionnaire we assessed habitual food and nutrient intake of patients with T2D aged ≥65 years, all of whom were Japanese and physically active, taking part in the KAMOGAWA-DM cohort study. Patients' body composition was evaluated by bioimpedance analysis. Sarcopenia was defined as having both a grip strength of <26 kg for men and <18 kg for women and a skeletal muscle mass index of <7.0 kg/m2 for men and <5.7 kg/m2 for women. Logistic regression analyses were used to investigate the effect of energy intake on the presence of sarcopenia in this cross-sectional study of 391 patients (205 men, 186 women). RESULTS: Fifty-five patients (14.1%) were diagnosed as having sarcopenia. Energy intake was significantly lower in patients with sarcopenia than without sarcopenia (mean ± SD [n = 366] 1498.8 ± 389.4 vs 1786.2 ± 706.7 kcal/d, respectively; P = 0.016). After adjusting for age, sex, exercise, smoking status, HbA1c, and body mass index, patients' energy intake (per 100 kcal) was negatively associated with the presence of sarcopenia (odds ratio 0.86; 95% confidence interval 0.78-0.95; P = 0.001). CONCLUSION: Energy intake was negatively associated with the presence of sarcopenia in elderly patients with T2D.

Sarcopenia is associated with tongue pressure in older patients with type 2 diabetes: A cross-sectional study of the KAMOGAWA-DM cohort study.

AIM: Death as a result of pneumonia is an important issue in patients with diabetes. Tongue pressure is associated with swallowing function, which has a close association with aspiration pneumonia. However, no previous studies have shown the association between sarcopenia and tongue pressure in older patients with type 2 diabetes. METHODS: In the present cross-sectional study, we investigated body composition, handgrip strength and tongue pressure. Skeletal muscle mass index (kg/m2 ) was defined as appendicular muscle mass / the square of the height. Sarcopenia was defined when both handgrip strength <26 kg for men and <18 kg for women, and the skeletal muscle mass index <7.0 kg/m2 for men and <5.7 kg/m2 for women existed. RESULTS: Among 144 patients (82 men, 71.4 years [SD 6.7 years]), 11.8% had sarcopenia. Tongue pressure was associated with skeletal muscle mass index and handgrip strength (r = 0.361, P < 0.001 and r = 0.387, P < 0.001, respectively, in men; and r = 0.300, P = 0.018 and r = 0.538, P < 0.001, respectively, in women). Tongue pressure was associated with the prevalence of sarcopenia after adjusting for covariates (OR 3.83, 95% CI 1.06-13.9, P = 0.041). According to the receiver operating characteristic curve analysis, the optimal cut-off value of handgrip strength for the presence of low tongue pressure was 27.7 kg (AUC 0.70, 95% CI 0.53-0.83, sensitivity 0.78, specificity 0.64) in men and 18.3 kg (AUC 0.71, 95% CI 0.54-0.84, sensitivity 0.82, specificity 0.54) in women. CONCLUSIONS: Sarcopenia, especially handgrip strength, is associated with tongue pressure in older patients with type 2 diabetes. We should consider a decrease of swallowing function when examining patients with sarcopenia. Geriatr Gerontol Int 2019; 19: 153-158.

Intake of Carbohydrate to Fiber Ratio Is a Useful Marker for Metabolic Syndrome in Patients with Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND/AIMS: The effect of low carbohydrate diet on human health is still controversial. Whole grain, which is carbohydrate rich in fiber, has protective effects on human health. Thus, we assumed that intake of carbohydrate to fiber ratio has an important role in human health. METHODS: This is a post-hoc analysis of a cross-sectional study of 164 patients with type 2 diabetes. Habitual food and nutrient intake were assessed and estimated by a self-administered diet history questionnaire. Intake of carbohydrate to fiber ratio was defined as carbohydrate (g)/fiber intake (g). Logistic regression analyses were performed to reveal the association between intake of carbohydrate to fiber ratio and metabolic syndrome (MetS). RESULTS: Intake of carbohydrate to fiber ratio has closely associated with metabolic parameters, including triglycerides (r = 0.21, p = 0.007) and high-density lipoprotein cholesterol (r = -0.23, p = 0.003). Intake of carbohydrate to fiber ratio was associated with MetS (OR 1.06 [95% CI 1.00-1.13], p = 0.047) after adjusting for covariates, whereas carbohydrate intake (1.00 [0.99-1.01], p = 0.752) or carbohydrate energy/total energy (1.00 [0.94-1.07], p = 0.962) was not associated with MetS. CONCLUSIONS: Intake of carbohydrate to fiber ratio was associated with MetS, whereas carbohydrate intake was not.

Late-night-dinner is associated with poor glycemic control in people with type 2 diabetes: The KAMOGAWA-DM cohort study.

Skipping breakfast or irregular breakfast is associated with poor glycemic control. However, a relationship between the timing of dinner and glycemic control in people with type 2 diabetes remains indefinite. Therefore, we investigated the relationship between late-night-dinner and glycemic control in people with type 2 diabetes. We performed questionnaire survey for lifestyle factors in this cross-sectional study. We defined having dinner later than eight pm as late-night-dinner. We examined the differences in clinical and metabolic parameters between those who have late-night-dinner and those who do not have. We also examined the relationship between late-night-dinner and HbA1c, using multiple regression analysis. Ninety-five people (23.2%) had a late-night-dinner, among 409 people with type 2 diabetes. Metabolic parameters (mean (SD) or median (interquartile range)) of people with late-night-dinner were worse than those of without, including body mass index (BMI) (24.4 (4.0) vs. 23.2 (3.4) kg/m2, p = 0.006), triglycerides (1.5 (1.1-2.1) vs. 1.2 (0.8-1.7) mmol/L, p < 0.001), HDL-cholesterol (1.4 (0.4) vs. 1.6 (0.4) mmol/L, p = 0.004) and hemoglobin A1c (58.1 (13.3) vs. 55.2 (10.2) mmol/mol, (7.5 (1.2) vs. 7.2 (0.9) %), p = 0.023)). Late-night-dinner (standardized regression coefficient = 0.13, p = 0.028) was associated with hemoglobin A1c after adjusting for age, BMI, sex, duration of diabetes, smoking, exercise, alcohol, snacking after dinner, nighttime sleep duration, time from dinner to bedtime, skipping breakfast, and medication for diabetes. Late-night-dinner is independently associated with poor glycemic control in people with type 2 diabetes.

Protein Intake, Especially Vegetable Protein Intake, Is Associated with Higher Skeletal Muscle Mass in Elderly Patients with Type 2 Diabetes.

BACKGROUND/AIMS: Protein intake is important for maintaining muscle mass in general population. However, it remains to be elucidated the association between dietary protein intake and skeletal muscle mass in elderly patients with type 2 diabetes. METHODS: In this cross-sectional study of 168 elderly patients with type 2 diabetes, we investigated the relationship between skeletal muscle index (SMI) and protein intake. Bioimpedance analysis was used for measurement for skeletal muscle mass (kg) and SMI (%), which was defined as skeletal muscle mass (kg)/total body weight (kg) × 100. Habitual food and nutrient intake were estimated by a questionnaire. RESULTS: Protein intake was independently correlated with SMI after adjusting for age, hemoglobin A1c, C-peptide index, exercise, smoking, insulin treatment, total energy intake, and C-reactive protein (standardized regression coefficient = 0.664, P < 0.001 in men and standardized regression coefficient = 0.516, P = 0.005 in women). Additionally, the animal protein to vegetable protein ratio was negatively correlated with SMI after adjusting for covariates in men (standardized regression coefficient = -0.339, P = 0.005). CONCLUSIONS: We found that total protein intake, especially vegetable protein intake, was positively associated with skeletal muscle mass in elderly patients with type 2 diabetes.

Urinary pH reflects dietary acid load in patients with type 2 diabetes.

Dietary acid load is important information, however, survey of food intake needs time and skill. Therefore, it is difficult to survey food intake from all patients. It remains to be elucidated the association between dietary acid load and urinary pH in patients with type 2 diabetes. In this cross-sectional study of 173 patients, we investigated the relationship between urinary pH and dietary acid load, assessed with potential renal acid load. Habitual food and nutrient intake was assessed by a self-administered diet history questionnaire. Urinary pH was negatively correlated with potential renal acid load (r = -0.24, p = 0.002). Multivariate regression analysis revealed that potential renal acid load (standardized regression coefficient = -0.21, p = 0.036) was associated with urinary pH after adjusting for covariates. In addition, according to the receiver operator characteristic analysis, the optimal cut-off point of urinary pH for high dietary acid load, defined as potential renal acid load over 7.0 mEq/day was 5.7 (area under the receiver operator characteristic curve 0.63 (95% CI 0.54-0.71), sensitivity = 0.56, specificity = 0.70, p = 0.004). Urinary pH was associated with dietary acid load in patients with type 2 diabetes. We suggest that urinary pH can be a practical screening marker for dietary acid load in patients with type 2 diabetes.